Relationships Among Pain, Depressed Mood, and Global Status in Fibromyalgia Patients: Post Hoc Analyses of a Randomized, Placebo-Controlled Trial of Milnacipran

BackgroundPatients with fibromyalgia often experience depressive symptoms in addition to chronic pain and other characteristic symptoms associated with this disorder.ObjectiveTo examine the relationships among pain, depressive symptoms, and global status in a clinical trial of milnacipran for fibromyalgia.MethodsData from a randomized, double-blind study (milnacipran 100 mg/d, n = 516; placebo, n = 509) were analyzed. Treatment outcomes included quantitative changes in pain and Beck Depression Inventory (BDI) scores, mean Patient Global Impression of Change (PGIC) scores, and three responder endpoints: patients with ≥30% pain improvement, PGIC score ≤2, and patients meeting both pain and PGIC responder criteria (2-measure composite responders). Correlations and path analyses were conducted to evaluate relationships among improvements in depressive symptoms, pain, and PGIC.ResultsPatients receiving milnacipran had greater decreases in mean pain scores, lower mean PGIC endpoint scores, and higher responder rates regardless of baseline severity of depressive symptoms. The highest responder rates were found in patients with greater than four-point improvement in BDI scores (milnacipran vs. placebo: pain, 57.5% vs. 39.0%; PGIC, 60.1% vs. 38.2%; 2-measure composite, 49.0% vs. 27.9%; all p < 0.01), although significant differences between treatment groups were also found in patients with no improvement or worsening of depressive symptoms. Correlations between changes in BDI and changes in pain or PGIC were low (r ≤ 0.3). Path analyses indicated 87.2% of pain reduction to be a direct effect of milnacipran treatment. Conclusion: Symptom improvements with milnacipran were only weakly associated with baseline depressive symptoms and were largely independent of improvements in depressive symptomatology.